1. Field of the Invention:
This invention relates to certain 1,6-dihydro-6-oxo-2-(ortho-substituted-phenyl)pyrimidine- 5-carboxylic acid derivatives and to their use as inhibitors of allergic reactions.
2. Description of the Prior Art:
Various medicinal agents have been employed in the treatment of allergic reactions such as bronchial asthma and allergic rhinitis which are believed to result mainly from antigenantibody interaction. With respect to bronchial asthma, one of the most serious of these allergically-mediated diseases, bronchodilators such as theophylline, isoproterenol, epinephrine and atropine are used primarily in providing symptomatic relief. These agents, however, have undesirable side effects, e.g. cardiac stimulation and gastrointestinal distress.
With the recent introduction of disodium cromoglycate described by J. S. G. Cox, et al. in Adv. in Drug Res., 5, 115-196 (1970), the physician has been provided with an agent which, when administered to asthmatic patients prior to inhalation of specific antigens, inhibits the release of mediators, e.g. histamine and SRS-A (slow-reacting-substance of anaphylaxis), believed to be responsible for the asthmatic response. While making possible a prophylactic treatment for bronchial asthma without cardiovascular side effects and thus representing a significant advance, disodium cromoglycate suffers from a major disadvantage in that it is not orally absorbed and must be administered by inhalation.
With respect to the 1,6-dihydro-6-oxo-2(substitutedphenyl)pyrimidine-5-carboxylic acid derivatives of the present invention, the following references illustrate structurally related compounds known in the art.
1. Preparation of the unsubstituted acid and ester of the formula ##STR1## where R is hydrogen or ethyl is disclosed by S. Ruhemann in Ber., 30, 821 (1897).
2. The p-methylphenyl and p-methoxyphenyl substituted esters and acids of the formula ##STR2## where R is hydrogen or ethyl and X is methyl or methoxy are disclosed by Mitter, et al. in J. Chem. Soc., 123, 2179 (1923) and Quart. J. Indian Chem. Soc., 2, 61 (1925).
3. Shen, et al., in U.S. Pat. Nos. 3,660,403 and 3,745,161 disclose compounds of the general formula ##STR3## where R[Ar] may inter alia be substituted phenyl, Y may be hydrogen and X is any of various substituents including hydroxy and alkoxy. The reference compounds are disclosed as having antiinflammatory, antipyretic and analgesic activity, and no mention is made of any utility as antiallergy agents. None of the compounds of the present invention is specifically disclosed in either of the Shen patents.
4. U.S. Patent 3,883,653 discloses antiallergy compounds of the formula ##STR4## where m is an integer of 0 or 1 and Ar is pyridyl, thienyl, furyl, phenyl or phenyl substituted by hydroxy, methyl, methoxy, nitro, chloro, fluoro, 3,4-dimethoxy, 3,4,5-trimethoxy or alkanoylamino. None of the compounds of the present invention are disclosed in this reference.